Objective Explore the mechanism of action of Kruppel-like factor 4 (KLF4) in the oxidative damage model of hippocampal neurons in mice induced by glutamate. Methods To clarify the role of KLF4 and glutamate in the oxidative toxicity of epilepsy, the mouse hippocampal neuron cell line (HT22) was adopted, and a neuronal death excitotoxicity cell model was formed by induction with glutamate as the in vitro epilepsy experimental model. The expression level of KLF4 was detected by Real-Time PCR. HT22 cells were transfected with KLF4-specific siRNA, and the experiments were grouped as follows: Ctrl group, Glu group, Glu + siKLF4-1 group, and Glu + siKLF4-2 group. The cell viability of each group was detected by the CCK8 method. Results KLF4 was significantly increased in the epilepsy model of HT22 cells induced by glutamate, while downregulation of KLF4 improved the proliferation and viability of neurons in the epilepsy model of HT22 cells induced by glutamate. Conclusion In the hippocampal neuron cells of epileptic mice, KLF4 is highly expressed. The downregulation of KLF4 improves the proliferation function and vitality of glutamate-induced HT22 cells, indicating that KLF4 may contribute to the occurrence and development of epilepsy by participating in the regulation of oxidative stress responses.
Citation:
YANG Yang, SUN Hongying, Celemuge, Cheliger. The mechanism of Krüppel-like factor 4 in glutamate-induced hippocampal neurons of epileptic mice. Journal of Epilepsy, 2025, 11(1): 41-44. doi: 10.7507/2096-0247.202411005
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- 1. Asadi-Pooya A A, Brigo F, Lattanzi S, et al. Adult epilepsy. The Lancet, 2023, 402(10399): 412-424.
- 2. Li X, Quan P, Si Y, et al. The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress. J Neuroinflammation, 2024, 21(1): 13.
- 3. Ghaleb AM, Yang VW. Krüppel-like factor 4 (KLF4): what we currently know. Gene, 2017, 611: 27-37.
- 4. 杨阳, 孙洪英. Krüppel样因子4在神经系统疾病中的作用研究进展. 癫痫杂志, 2024, 10(2): 141-146.
- 5. Akyuz E, Polat A K, Eroglu E, et al. Revisiting the role of neurotransmitters in epilepsy: an updated review. Life sciences, 2021, 265: 118826.
- 6. Parsons ALM, Bucknor EMV, Castroflorio E, et al. The interconnected mechanisms of oxidative stress and neuroinflammation in epilepsy. Antioxidants, 2022, 11(1): 157.
- 7. Chen Y, Chen J, Chen Y, et al. miR-146a/KLF4 axis in epileptic mice: a novel regulator of synaptic plasticity involving STAT3 signaling. Brain Research, 2022, 1790: 147988.
- 8. 许文博. 条件性KLF4敲除小鼠的建立及癫痫分子发病机制研究. 吉林大学, 硕士学位论文, 2022.
- 9. Zhu S, Tai C, MacVicar BA, et al. Glutamatergic stimulation triggers rapid Krüpple-like factor 4 expression in neurons and the overexpression of KLF4 sensitizes neurons to NMDA-induced caspase-3 activity. Brain Res, 2009, 1250: 49-62.
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